Several genetic, environmental, lipid partitioning, and biochemical factors, shown on the left, promote the development of subclinical inflammation and insulin resistance, both of which can exacerbate each other. Several genetic, environmental, lipid partitioning, and biochemical factors, shown on the left, promote the development of subclinical inflammation and insulin resistance, both of which can exacerbate each other. This is the postulated driving mechanism that leads to the development of classic components of the metabolic syndrome, shown on the right. Both the classic definitions and the addition of the predisposing and promoting factors can contribute to risk assessment of the individual patients in regard to existing comorbidities and to future cardiovascular and diabetes risk. CRP, C-reactive peptide; CVD, cardiovascular disease; GDM, gestational diabetes mellitus; IL-6, interleukin-6; IMCL, intramyocellular lipid; NAFLD, nonalcoholic fatty liver disease; PAI-1, plasminogen activator inhibitor 1; PCOS, polycystic ovarian syndrome; SGA, small for gestational age; T2DM, type 2 diabetes; TG, triglycerides. Ram Weiss Dia Care 2011;34:S171-S176 ©2011 by American Diabetes Association